This invention relates to pressure sensitive adhesive materials having particular utility in the medical field, for example for use with wound dressings and ostomy appliances.
Pressure sensitive adhesive materials are used in many medical device fields and are made into products such as tapes, bandages, surgical drapes, IV dressings and the like. Hydrocolloid pressure sensitive adhesives are medically useful adhesives that have been known for about 30 years and were originally developed as bandages for the oral cavity to aid in delivery of drugs to the gingiva. Hydrocolloid adhesives have been hitherto unique in that they are inherently adhesive and inherently absorbent. They are useful as wound dressings because they can be applied directly to open wounds and secured on the surrounding intact skin, and as skin barriers because they protect the peristomal skin of ostomy patients. Many hydrocolloid skin barriers are known and are used for these purposes. It is convenient to-divide these into xe2x80x9cintegratedxe2x80x9d compositions and xe2x80x9cnon-integratedxe2x80x9d compositions. In this context, xe2x80x9cintegratedxe2x80x9d means those compositions which substantially, retain their dimensional stability and form when saturated with wound exudate and/or other body fluid. xe2x80x9cNon-integratedxe2x80x9d means those compositions which become soft gels and amorphous as they become saturated with fluid.
Particularly in the area of wound dressings, the known hydrocolloid adhesives have a number of limitations. First, the absorption capacity of hydrocolloid dressings is normally insufficient to handle the large amount of exudate from certain especially chronic wounds. Second, hydrocolloid compositions, by definition, contain water soluble absorbents, which provide xe2x80x9cwet tackxe2x80x9d to the composition, and these leach out into the wound and may be absorbed into the body. Third, hydrocolloid compositions are normally opaque, and so the healing of the treated wound cannot be assessed until the dressing is changed. Fourth, the continuous phases used in many especially non-integrated hydrocolloid adhesives contain substantial quantities of low molecular weight elastomers such as polyisobutylene. The polyisobutylene is dispersed in the soft gel from a non-integrated hydrocolloid composition which remains in the wound after dressing removal. While the polyisobutylene is chemically saturated and thus inert, it is nevertheless thought that it may be incorporated into the growing cellular structure in, for example, healing chronic wounds and the polyisobutylene has been suggested as the cause of abnormal xe2x80x9cfoam cellsxe2x80x9d observed in the histology of such dermal tissues. Although these foam cells are not thought to be permanently harmful, it is important to eliminate any leachable material from these medically useful compositions.
The first hydrocolloid compositions to be described were non-integrated. U.S. Pat. No. 3,339,546 discloses compositions which are inelastic, and which are non-integrated, i.e. which do not maintain their dimensional stability and become amorphous when imbibed with wound fluid or other body fluid. A typical formulation taught by this prior art is the composition formed from low molecular weight polyisobutylene (40% by wt.), pectin (20% by wt.), sodium carboxymethyl cellulose (20% by wt.) and gelatine (20% by wt.). This formulation was used as a dressing for the gingiva but is also believed to be the basis of commercially successful skin barrier and wound care products. Such compositions form a soft gel when in contact with an exuding wound, and the resultant gel remains in the wound when the dressing is removed. This lack of integrity is a drawback. The remaining gel must be irrigated from the wound by the nurse who is performing the change of dressing, and this is both time consuming for the nurse and painful for the patient.
Notwithstanding the drawbacks of this prior art bandage, however, the compositions taught by U.S. Pat. No. 3,339,546 are extremely gentle to the intact skin. This is thought to be due to a number of factors. First, the compositions of this patent contain a relatively small number of components. On a statistical basis therefore, a fewer number of skin reactions can be expected. Second, the ingredients are usually food components or additives, and have a long history of use. Third, polyisobutylene contains a chemically saturated aliphatic carbon-carbon backbone, and therefore needs no stabiliser to reduce the degradation often seen in rubbery materials having chemical unsaturation in the backbone. Fourth, the compositions apparently maintain the skin moisture at an optimum level, by absorbing excess perspiration and reducing the amount of skin maceration that is normally associated with the wearing of a wound dressing for several days. Skin maceration leads to a reduction in the mechanical strength of the skin, and in turn leads, on removal of the bandage, to increased skin damage to the healthy skin surrounding the margin of the wound. This is often termed xe2x80x9cmechanical irritationxe2x80x9d. The prior art compositions described below achieve the integration of the continuous phase for the most part at the expense of the gentle, xe2x80x9cskin-friendlyxe2x80x9d character displayed by the compositions of U.S. Pat. No. 3,339,546.
The lack of integrity was a serious drawback in the use of dressings and barriers based on these early hydrocolloid compositions and much development was completed in efforts to overcome the deficiency. Thus, British Patent 1,576,522, corresponding to U.S. Pat. No. 4,231,369 describes improved hydrocolloid compositions that are integrated. There is provided a sealing material for ostomy use consisting of a hydrocolloid dispersed in a continuous phase of styrene-isoprene-styrene copolymer, or other thermoplastic elastomer such as an ethylene-propylene copolymer. Also present is a hydrocarbon tackifier and optionally an oil extender and an antioxidant. This material is said to have the advantage of being elastomeric and flexible, and thus bandages made from it should adhere well to the skin and be conformable. Because of the styrene-isoprene-styrene block copolymer the composition is integrated. The styrene-isoprene-styrene block copolymer forms physical cross links within the continuous phase at room temperature. This is because the polystyrene segments within the copolymer are incompatible with the polyisoprene segments, and they associate at room temperature to glassy domains which act as the physical cross links to form a three dimensional lattice. However, because of the larger number of components, and in particular the tackifying resin and stabilisers, the material does tend to experience more complaints with irritation than does the material from U.S. Pat. No. 3,339,546. Also, because the hydrocolloid absorbent components in British Patent 1,576,522 are normally at a lower concentration in the final formulation than are the hydrocolloid components in U.S. Pat. No. 3,339,546, a lower absorption level is obtained. The absorption rate is also slower, because the integrated nature of the composition makes that lower level of chemical hydrocolloid components even more slowly accessible to the body fluid.
The shortcomings of barriers and dressings based upon formulae such as are described in U.S. Pat. No. 3,339,546 are also recognised by both U.S. Pat. Nos. 4,477,325 and 4,738,257. These two later patents disclose barriers and dressings based on an integrated formulation containing a continuous phase composed of a blend of high vinyl acetate EVA copolymer (51% wt. VA and 49% wt. ethylene) and low molecular weight polyisobutylene, in which is dispersed a discontinuous phase containing a blend of a superabsorbent material, pectin and sodium carboxymethyl cellulose. The function of the EVA copolymer is to cross link in the presence of ionising radiation, such as gamma radiation at a dosage of, for example 25 KGy, which would be used to sterilise dressings formed from the compositions of the invention. The cross linked network is formed essentially from the EVA polymer by irradiation of the EVA containing elastomeric phase. The problem with this type of system is that the dose from such a sterilisation process is widely variable in practice. A company offering services for the sterilisation of medical devices to a nominal dose of 25 KGy would typically specify a dose within the range of say 25-35 KGy, so that some dressings would receive close to the lower amount while some would receive the higher amount. It will readily be appreciated that such variation will lead to a variable cross link density within different dressings of even the same production batch, which in turn will lead to variable performance in terms of rate and capacity of fluid absorption.
U.S. Pat. No. 4,551,490 describes integrated hydrocolloid adhesives modified by diluting the amount of styrene-isoprene-styrene block copolymer present in the composition. The patent provides a medical grade pressure sensitive adhesive composition comprising a heterogeneous mixture of one or more polyisobutylenes or blends of polyisobutylenes and butyl rubber, one or more styrene radial or block copolymers, a tackifier, mineral oil and one or more water soluble and/or swellable hydrocolloid gums. It is believed that the polyisobutylenes, butyl rubber, mineral oil and tackifier serve to modify and plasticise predominantly the isoprene segment of the block/radial copolymer. In particular, the mineral oil is said to provide increased extensibility and aggressiveness of the adhesive. It is believed that the teachings of this patent form the basis of the commercially available hydrocolloid dressing products DuoDerm and Signa Dress. However, it has been found that the rates of absorption of saline with these compositions is very slow, and not very reproducible, and moreover very much less than the absorption levels available within the compositions of U.S. Pat. No. 3,339,546.
All prior art cited above is believed to form the basis of commercially available hydrocolloid dressings and skin barriers. All the prior art discussed above discloses modifications to the continuous phase to achieve integrated compositions. The integrated continuous phase is achieved in each case only at the expense of one or other of the beneficial properties of the non-integrated composition described in U.S. Pat. No. 3,339,546.
The prior art cited above seeks to improve the integrity of hydrocolloid type compositions by modifying the continuous phase. A different approach was taken in the art described in U.S. Pat. No. 4,192,785, which describes incorporating into the hydrocolloid discontinuous phase a cohesive strengthening agent such as natural or synthetic fibrous material and other insoluble absorbent polymers to integrate this phase. The cohesive strengthening agent functions in the adhesive composition by decreasing the tendency to tearing and by decreasing the tendency to erosion and disintegration by biological fluids. Thus the swelling of the hydrocolloids is controlled.
U.S. Pat. No. 4,952,618 discloses adhesives containing preferably water soluble polycationic hydrocolloids such as a chitosan salt and DEAE Dextran mixed with polyanionic and neutral hydrocolloids such as pectin and gelatin, respectively. These compositions are said to possess high integrity.
However, the continuous phases described in both the above patents are xe2x80x9cconventionalxe2x80x9d in that they are similarly composed preferably of a mixture of low molecular weight polyisobutylene and high molecular weight rubberxe2x80x94butyl rubber in U.S. Pat. No. 4,192,785 and high molecular weight polyisobutylene rubber in U.S. Pat. No. 4,952,618 respectively.
The present invention consists in a pressure-sensitive adhesive material comprising a mixture of (a) a continuous phase formed from a physically cross-linked solid rubber and a compatible liquid rubber; and (b) 10-70% by weight, based on the total adhesive material of a discontinuous phase comprising one or more hydrophilic polymers that are soluble and/or swellable in water.
The adhesive material of the present invention has an integrated continuous phase that can overcome some of the problems associated with the prior art. The pressure sensitive adhesives have the advantage over the prior art integrated adhesives that they do not require the presence of materials known to irritate skin and mucous membranes and they have a low propensity for allergic reaction. Compositions may be formulated within the scope of the invention that have no leachable components that would contaminate a healing wound, and they can be used in wound care, ostomy care and other medical products. By judicious choice of ingredients within the scope of the invention, compositions can be formulated that are relatively clear or translucent, and so are able to allow a visual assessment of the healing progress and the condition of a wound under a dressing. The content of resinous materials should not exceed 15% by weight, preferably 5% by weight, and in the more preferred embodiments of the invention resinous materials are avoided altogether, but other rubbers and, additives such as mineral oil and low molecular weight polymers may be present.
Compositions can be made according to the invention that are integrated but have absorption rates and capacities comparable with those observed for non-integrated compositions.
The present invention also provides barriers and wound dressings comprising a layer of the absorbent adhesive defined above coated on a non-adhesive, waterproof film. This construction is useful in a number of ways. One of these is for bandaging purposes, especially on movable body parts such as joints or on curved surfaces of the body. Wounds such as blisters, burns, venostasis ulcers and decubitus ulcers may advantageously be treated with the products of the invention. Another important use is for the protection of the skin around body openings, especially around the surgically created openings known as colostomies, ileostomies and urostomies.
A fluid absorbing adhesive according to the invention comprises a continuous phase consisting of one or more solid, physically cross linked thermoplastic elastomer components such as styrene-olefin-styrene and/or styrene-alkane-styrene copolymers and a liquid rubber component which, at least in preferred embodiments, is substantially resin free. The continuous phase provides xe2x80x9cdry tackxe2x80x9d to adhere the adhesive to dry, i.e. not moist, skin. Dispersed within the continuous phase is a discontinuous phase consisting substantially of absorbent polymer. Useful as the absorbent polymer are for example insoluble calcium alginate and synthetic insoluble absorbents such as crystalline sodium carboxymethyl cellulose. Water-soluble hydrocolloids may also be used for this phase.
The continuous phase may include solid rubbers such as linear or radial A-B-A block copolymers or mixtures of these A-B-A block copolymers with simple A-B block copolymers. However, the proportion of A-B block copolymers, relative to the A-B-A block copolymers should not normally exceed 85% by weight and lower amounts such as 10 to 50% by weight would normally be used. These block copolymers can be based on styrene-butadiene, styrene-isoprene, and hydrogenated styrene-diene copolymers such as styrene ethylene-butylene.
Suitable styrene-diene copolymers for the practice of the invention are exemplified by a blend of linear styrene-isoprene-styrene triblock copolymer and linear styrene-isoprene diblock copolymer. Such a material is available from Shell Chemical as Kraton D-1161 and has a bound styrene content of about 15% and a diblock content of 17%. A second example is a blend of linear styrene-isoprene-styrene triblock copolymer and linear styrene-isoprene diblock copolymer available from Shell Chemical as Kraton D-1117 and which has a bound styrene content of about 17% and a diblock content of 33%.
An example of a suitable hydrogenated styrene-diene copolymer is a thermoplastic elastomer comprising a blend of clear linear triblock and diblock copolymer based on styrene and ethylene-butylene with a bound styrene of 14% mass. Such a material is commercially available from Shell Chemical Company as Kraton G-1657. Another example is Kraton G-1652 from Shell Chemical Company, which is a thermoplastic elastomer comprised of a clear linear triblock copolymer based on styrene and ethylene-butylene, S-E/B-S, with a bound styrene content of about 30% by weight. Also suitable are polymers in which there is a combination of chemically saturated blocks and chemically unsaturated blocks. For example, a branched copolymer consisting of two polyisoprene chains attached to the rubber midblock of a styrene/ethylene-butylene/styrene triblock copolymer. Such a material is available from Shell Chemical Company as Kraton Research Product RP6919. This material has a styrene content of 18%, and isoprene content of 36% and an ethylene-butylene content of 46% by weight. Also, a low styrene synthetic copolymer of butadiene and styrene, commonly called SBR rubber, can be used as a solid rubber.
Liquid rubbers useful-in the invention include synthetic liquid isoprene rubber, depolymerised natural rubber, various functionally terminated synthetic liquid isoprene-styrene rubbers and liquid isoprene rubbers, liquid isoprene-styrene copolymer, liquid isoprene-butadiene copolymer, liquid butadiene-styrene copolymer and hydrogenated versions of these materials such as liquid ethylene-propylene-styrene. These liquid rubbers are characterised in that they are completely compatible with the solid rubber. The liquid rubbers typically have a molecular weight of 25000 to 50000, a glass transition temperature of less than xe2x88x9250xc2x0 C., and a viscosity at 38xc2x0 C. of 50 to 10000 Pas. A block copolymer of styrene and isoprene having a styrene content of about 13% and an isoprene content of about 87%, a glass transition of about xe2x88x92600xc2x0 C., a melt viscosity of about 240 Pas at 50xc2x0 C. and which is commercially available from Shell Chemical Company as LVSI-101, is particularly useful in the practice of the invention. Within the continuous phase, the preferred weight ratio of solid rubber to liquid rubber is in the range from 1:0.5 to 1:7, and is varied in order to obtain the desired degree of adhesiveness and tackiness.
Other materials may be added to the continuous phase to modify the properties for certain uses. Materials such as low molecular weight polybutenes, commercially available under the tradenames Parapol 1300 (Exxon) or Hyvis 30 (BP), low molecular weight polyisobutylene, rubbers such as butyl rubber and high molecular weight polyisobutylene, mineral oil, and small amounts of other optional ingredients may be added. The optional low molecular weight polyisobutylene may be selected from one or more low molecular weight polyisobutylenes having a viscosity average molecular weight of from 36,000 to 70,000. Such polyisobutylenes are commercially available under the trademark Vistanex from Exxon Chemical as grades LMMS, LMMH and LMH, having viscosity average molecular weights of about 45,000, 53,000 and 63,000 respectively. The optional low molecular weight polyisobutylene may be present in an amount corresponding to from 0% wt. to about 80% weight of the continuous phase. Optionally, an elastomeric polymer such as butyl rubber or high molecular weight polyisobutylene may also be blended into the continuous phase. The optional butyl rubber may be used in the viscosity average molecular weight range of 200,000 to 600,000 and is exemplified by the grades Butyl 065 or Butyl 077, both available from Exxon Chemical. The optional high molecular weight polyisobutylene may be used in the viscosity average molecular weight range of 800,000 to 2,500,000 and is exemplified by the Vistanex MM series of products, available from Exxon Chemical, with the MM L-80 grade being a preferred grade for the optional high molecular weight polyisobutylene. The optional high molecular weight rubbers, blended as is indicated above, may be added in amounts suitable to modify various properties of the final formulation and may be from 0% to about 50% of the total weight of the continuous phase. The optional low molecular weight polybutenes and/or mineral oil may be added in amounts from 0% to about 20% of the weight of the continuous phase.
The addition of polymer stabilisers can be advantageous, to protect an unsaturated elastomer from degradation during processing. Suitable stabilisers useful in the practice of the invention include those normally indicated for use with styrene-olefin-styrene block copolymer thermoplastic elastomers such as organophosphites and the so-called hindered phenols, but any suitable stabilisers may be employed. An example of an organophosphite stabiliser is tris(nonylphenyl) phosphite, available as Polygard HR, manufactured by Uniroyal. Particularly useful are the hindered phenols, Irganox 1010 and Irganox 565, manufactured by Ciba. Irganox 1010 is benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-2,2-bis[[3-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenol]-1-oxopropoxy]methyl]-1,3-propanediyl ester. Irganox 565 is phenol, 4-[[4,6-bis(octylthio)-1,3,5-triazine-2-yl]amino]-2,6-bis(1,1-dimethylethyl)-. Stabilisers may be used separately or in combination, and suitable ranges are within 0.3-1.5% by weight based on the total formulation. The stabilisers are always added to the continuous phase, as is shown in the examples.
The discontinuous phase comprises one or more hydrophilic polymers that are soluble or which absorb and/or are swellable in water. One or more such polymers may be present and a mixture of soluble and insoluble polymers can be used. Suitable swellable polymers include cross-linked sodium carboxymethyl cellulose, crystalline sodium carboxymethylcellulose, cross-linked dextran and starch-acrylonitrile graft copolymer. The swellable polymer may also be a so-called xe2x80x9csuper absorbentxe2x80x9d material such as starch sodium polyacrylate. Other hydratable polymers such as gluten and polymers of methyl vinyl ether and maleic acid and derivatives thereof may also be included in the discontinuous phase.
The discontinuous phase may also comprise one or more water-soluble hydrocolloids, alone or blended with one or more swellable polymers. Such soluble hydrocolloids include naturally derived products such as pectin, gelatin, starches, guar gum, locust bean gum, gum arabic, collagen, karaya gum, alginic acid and its sodium and/or calcium salts. Also useful are the synthetic hydrocolloids such as sodium carboxymethyl cellulose, cross linked sodium carboxymethyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, high molecular weight polyethylene glycols and polypropylene glycols.
The amount of hydrophilic polymer phase may be from 10% to 70% of the total weight of the adhesive, normally from 20% to 55% of the total adhesive by weight.
The hydrophilic polymer functions as the absorbent, and to provide the xe2x80x9cwet tackxe2x80x9d that ensures the adhesive adheres to the skin and to mucous membranes when they are moist. The hydrophilic polymer must be capable of swelling in water, and transporting water.
Other optional ingredients such as silica and optional active ingredients such as growth factors, antimicrobial compounds and wound-healing components such as collagen may also be incorporated into the compositions of the invention.
The adhesive compositions of the invention may be prepared as follows. The solid rubber, for example a styrene-olefin-styrene copolymer and the liquid rubber component are blended together in a suitable mixer, normally a sigma blade mixer with an extruder discharge. The mixer is heated to about 170xc2x0 C. A nitrogen flow of about 60 ml/sec through the mixer reduces the possibility of oxidative degradation of the rubber during processing. About 1% phr of a suitable stabiliser, say Irganox 1010 available from Ciba-Geigy, can be added at this stage. Normally a small amount of the liquid rubber, say 10-20%, is added to the whole amount of the solid rubber and the liquid rubber is allowed to blend with the soft solid rubber. When all this 10-20% of the liquid rubber has been absorbed, another portion of the liquid rubber is added, say 20-30%, and the liquid rubber is absorbed into the styrene-olefin-styrene rubber. This is continued until all the liquid rubber is added, when a pourable tacky intermediate adhesive is obtained. The mixer blades are stopped, the direction of the screw is reversed, and the intermediate adhesive is removed from the mixer. It is run off into suitably release coated containers and allowed to cool. The mixer is stabilised at 90xc2x0 C. and the powdery ingredients are charged to the mixer and the other optional ingredients, if present, can be added, and blended-in for a period of time. After mixing at 90xc2x0 C. for 20-30 minutes, the mixer temperature is raised to 105xc2x0 C., and the ingredients of the continuous phase, intermediate hot melt and other low and high molecular weight rubbers if present, can then be added. If high molecular weight rubbers are used, they may need to be premasticated in the mixer, or premilled on a rubber mill. Mixing is continued normally for a further 30 minutes or so. The fully mixed mass is then removed from the mixer and then extruded or pressed to the desired thickness, and then laminated to suitable substrates.
The invention will be further illustrated by means of the following examples.